Early Cancer Detection & Prognosis through Glycomics

早期癌症检测

• 批准号: 7480452
• 负责人: Milos Novotny
• 金额: $ 37.34万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-08 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7480452
• 关键词: Aftercare; Antibodies; Arts; Bioinformatics; Biological; Biological Markers; Cancer Patient; Capillary Electrophoresis; Class; Clinical; Colon Carcinoma; Complex; Data; Development; Diagnostic; Disease Progression; Disease remission; Evaluation; Excision; Female; Hand; Health; Human; Individual; Isomerism; Laboratories; Lectin; Link; Lung; Malignant Neoplasms; Maps; Measurement; Methodology; Microfluidics; Monitor; Numbers; Ovarian; Patients; Pattern; Pharmaceutical Preparations; Phase; Phase III Clinical Trials; Polysaccharides; Procedures; Process; Prostate; Proteins; Research; Research Personnel; Sampling; Screening for cancer; Screening procedure; Serum; Staging; Structure; Technology; Validation; analytical tool; base; cancer type; clinically relevant; comparative; glycosylation; male; outcome forecast; phase change; prognostic; programs; tool; trend; tumor progression

DESCRIPTION (provided by applicant): Rather than looking for specific cancer biomarkers (proteins or glycosylated proteins), we emphasize quantitative deglycosylation (removal of glycans) in unfractionated biological samples and displaying the removed glycans in quantitative glycan maps. Comparing glycomic profiles originating from healthy and diseased individuals should allow the assignment of structural changes associated with cancer. On the other hand, prognosis or a differential assessment of patients' health then relies on the isotopically-aided quantitative MS measurements of such glycan patterns. In the first two phases of our proposed research, clinically relevant samples will be screened through our well-established procedures while using the state-of- the-art MS-based methodologies and capillary electrophoresis. In Phase 1, the glycomic patterns of human blood serum collected from healthy females and males will be compared to those collected from ovarian, prostate, lung and colon cancer patients. Through bioinformatic and statistical evaluation a list of glycan markers that are associated with each type of cancer or with all types of cancer to be studied will be determined. This is necessary to establish quantitative trends in glycosylation or the occurrence of "glycosylation aberrations" and link these measurements to positively identified glycan structures. Glycomic profiles acquired for the same samples by CE-LIF will aid in determining changes that are due to changes in structural isomers which cannot be determined through MS. In Phase 2, the glycomic maps of human blood serum of cancer before and after treatment with a specific drug will be compared. In this phase, changes in the set of glycans defined in Phase 1 will be closely monitored and their changes as a result of cancer progression or remission will be evaluated. Phase 2 results will confirm or refute the potential glycan structures that will be defined as potential biomarkers in Phase 1. Upon the identification of these specific glycan changes or the set of glycan structures that change as a result of disease progression or remission, the potential of a faster screening approach such as lectin or antibody microarrays will be investigated. This is the aim of Phase 3 of this study which will focus on defining the best analytical tools that could be utilized as diagnostic and prognostic tool.

描述（由申请人提供）：我们不再寻找特定的癌症生物标志物（蛋白质或糖基化蛋白），而是强调在未分离的生物样品中定量脱糖基化（去除聚糖），并在定量的Glycan映射中显示去除的聚糖。比较源自健康和患病个体的糖基谱，应允许分配与癌症相关的结构变化。另一方面，对患者健康的预后或差异评估依赖于这种聚糖模式的同位素辅助定量MS测量。在我们提出的研究的前两个阶段中，在使用基于最先进的MS方法和毛细血管电泳的同时，将通过我们建立的程序进行临床相关样品。在第1阶段，将将从健康雌性和雄性收集的人血清的血清模式与从卵巢，前列腺，肺癌和结肠癌患者中收集的果胶模式进行比较。通过生物信息学和统计评估，将确定与每种类型的癌症或所有类型的癌症相关的聚糖标记列表。这对于建立糖基化或“糖基化畸变”的发生的定量趋势是必要的，并将这些测量结果与正面鉴定的聚糖结构联系起来。通过CE-LIF获得的同一样品获得的胶囊曲线将有助于确定由于无法通过MS确定的结构异构体变化而引起的变化。在第2阶段，将比较用特定药物治疗前后人类血清癌症血清的血清图。在此阶段，将密切监测阶段1中定义的聚糖集的变化，并将评估它们因癌症进展或缓解而变化。第2阶段的结果将确认或驳斥将在第1阶段定义为潜在生物标志物的潜在聚糖结构。在鉴定这些特定的聚糖变化或由于疾病进展或缓解而变化的聚糖结构集后，将研究更快的筛查方法，例如肠lectin或抗体微观阵列。这是本研究第3阶段的目的，它将着重定义可以用作诊断和预后工具的最佳分析工具。